Manipulation of PD‐L1 Endosomal Trafficking Promotes Anticancer Immunity

• DOI: 10.1002/advs.202206411
• Publication Date: 2022-12-26T03:53:06Z
• Authors: Zuodong Ye; Yiding Xiong; Wang Peng; Wenjie Wei; Lihong Huang; Juliana Yue; Chunyuan Zhang; Ge Lin; Feng Huang; Liang Zhang; Songguo Zheng; Jianbo Yue
• Keywords: 0301 basic medicine; Science; Q; Cell Membrane; Endosomes; B7-H1 Antigen; 3. Good health; 6J1; anticancer immunity; 03 medical and health sciences; endosomal trafficking; PD‐L1; Neoplasms; Tumor Microenvironment; endocytosis; Humans; extracellular vesicle; Research Articles; T-Lymphocytes, Cytotoxic

Abstract The aberrant regulation of PD‐L1 in tumor cells remains poorly understood. Here, the authors systematically investigate endosomal trafficking plasma membrane cells. They show that is continuously internalized, and then trafficked from early endosomes to multivesicular bodies/late endosomes, recycling lysosomes, and/or extracellular vesicles (EVs). This constitutive endocytic Rab5‐ clathrin‐dependent. Triazine compound 6J1 blocks induces its accumulation by activating Rab5. also promotes exosomal secretion Rab27. Together, these effects result a decrease level 6J1‐treated enables be more susceptible tumor‐killing activity T vitro. increases tumor‐infiltrating cytotoxic chemokines microenvironment. Rab27 knockdown abolishes 6J1‐induced EVs revokes exhausted tumors, thereby improving anticancer efficacy 6J1. Furthermore, combination an anti‐PD‐1 antibody significantly improves immune response. Therefore, manipulating provides promising means promote response addition checkpoint‐blocking therapy.